The objective of this proposal is to (1) determine whether immune suppression encountered during chemotherapy with 5-fluorouracil (5-FU), cytosine arabinoside (Ara-C) or cyclophosphamide (CY) results from toxicity to precursors of functional antibody-forming B cells, and cytotoxic lymphocytes (CTL) or to the ancillary cells known to be necessary for helping/amplifying development of a maximal immune response. (2) Can the defect, if shown to be lack of helping/amplifying lymphoid cell(s), be overcome by replacement with a normal population of this lymphoid cell lineage resulting in rescue of functional B- and T-cell effector cell precursors which are resilient to the therapy? (3) If the defect can be replaced by normal lymphoid populations, can known, currently available factors, which replace helper/amplifier requirements, replace the lymphoid cell? The goal of the program will be the development of treatments or procedures which effectively restore immune competence to hosts where the immune system is compromised by chemotherapy. We have chosen 5-FU and Ara-C because they have been shown to cause regression of tumor mass in humans and experimental animals. The immune suppression encountered by these agents is without general suppression of hematopoietic function; clonable B-cells, progenitors of megakaryocyte and granulocyte levels, are normal after therapy. This suggests the immune suppression encountered during administration of these agents occurs at the level of cell-cell interaction required for effective expression of specific immune functions. In vitro culture techniques will be used to delineate the specific ancillary cell defect arising during chemotherapy. Antibody responses against T-dependent SRBC and T-independent TNP-LPS will be monitored after therapy. Primary versus secondary in vitro CTL responses will be measured. If ancillary cell defects account for immune suppression, IgG and primary CTL responses will be absent while T-independent TNP-LPS and secondary CTL responses will be unaffected by therapy.